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Biomedical subjects

T Miwa

Publications and source records attributed to T Miwa.

At least 109 records · Page 6Linked to original sources

Activation of 11 beta-hydroxysteroid dehydrogenase by dehydroepiandrosterone sulphate as an anti-hypertensive agent in spontaneously hypertensive rats.

The anti-hypertensive properties of dehydroepiandrosterone sulphate (DHEAS) have been investigated by studying its effects on blood pressure, on serum concentrations of corticosterone and dehydrocorticosterone, and on 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity in spontaneously hypertensive rats (SHR). SHR were given intraperitoneal injections of DHEAS (10 mg day-1 for 70 days) from six to 16 weeks of age. The blood pressure-time curve was significantly (P < 0.05) suppressed immediately after administration of DHEAS. There was no difference between the heart rates of control and DHEAS groups. Serum concentrations of corticosterone and dehydrocorticosterone in the DHEAS group were significantly (P < 0.05) lower than those of the control group. The dehydrocorticosterone/corticosterone concentration ratio was, however, significantly (P < 0.05) higher in the DHEAS group, suggesting that treatment with DHEAS enhanced the overall interconversion of corticosterone to dehydrocorticosterone. The activity of 11 beta-HSD in specific organs of the DHEAS group was affected, characteristic changes being increases in the kidney (14-58%), decreases in the liver (11-27%) and no change in the testis. Direct addition of DHEAS to 11 beta-HSD preparations from the kidneys of control SHR had the same effect as that observed in the in-vivo experiments. The fall in serum corticosterone in the DHEAS group is considered to be related, at least partly, to increased activity of kidney 11 beta-HSD. The inverse correlation of kidney 11 beta-HSD activity with serum corticosterone and blood pressure (-r = 0.628, P < 0.01, and -r = 0.478, P < 0.05, respectively) suggest that DHEAS delayed the development of hypertension in SHR by selective promotion of kidney 11 beta-HSD activity which in turn resulted in lower serum concentrations of corticosterone and its minimal aldosterone-like activity.

11-beta-Hydroxysteroid Dehydrogenases↗

Protein kinase C gene expression in dispersed guinea-pig gastric parietal cells.

BACKGROUND AIMS: It has been implicated that protein kinase C (PKC) is involved in gastric acid secretion. The purpose of this study is to examine whether mRNA expression of PKC isoforms is observed in guinea-pig gastric parietal cells, and whether such PKC expression is regulated by agonists that stimulate gastric acid secretion. METHODS: Expression of PKC mRNA was assessed using isolated guinea-pig gastric parietal cells treated with or without three kinds of agonists by Northern blot analysis. RESULTS: (1) alpha, gamma and zetaPKC mRNAs were expressed in guinea-pig gastric parietal cells; (2) both carbachol and gastrin increased the level of alpha and gammaPKC mRNAs, but synthesis of zetaPKC mRNA was not affected by these agonists, and (3) histamine did not affect the expression level of alpha, gamma and zetaPKC mRNAs. CONCLUSION: alpha and gammaPKC isoforms may be involved in the regulation of gastric acid secretion.

Animals↗

[Study of the function of nerve growth factor in the olfactory tract of the mouse].

The aim of this study was to examine the function of nerve growth factor (BGF) in the olfactory tract of mice. Using the mice which had received unilateral olfactory bulbectomy and in which antibodies to NGF had been continuously infused with into the contralateral olfactory blub, three kinds of analysis were performed: histological analysis of the olfactory epithelium by HE staining, immunohistochemical analysis of the olfactory epithelium using polyclonal antibodies to trk which forms the NGF receptor, and olfactory-mediated behavioral analysis with cycloheximide. These animals had been sacrificed at day 1, 3, 7, 14, 21 or 28. Several findings were obtained as a result of the above analysis. Degeneration of the olfactory epithelium and trk expression by the olfactory cells were observed on day 7, and the olfactory epithelium was incompletely regenerated on day 28. However, trk expression by the olfactory cell was still recognized and the olfactory function was not restored by day 28. These examinations suggest that NGF produced in the olfactory bulb was transported retrogradely to olfactory cells through the olfactory nerves, and was associated with sustaining the existence of those cells and with regenerating the olfactory tract after injury.

Animals↗

Factors affecting depth of gastric ulcers.

PURPOSE: We investigated the differences in background factors, clinical features, and gastric function tests among gastric ulcers of various depths. PATIENTS AND METHODS: The subjects were 68 patients (male 64, female 4) who were diagnosed as having a gastric ulcer at the angulus. The ulcers were classified according to depth based on the following: UL2 (shallow) ulceration to the submucosa; UL3 (intermediate), to the muscularis propria; and UL4 (deep excavation), beyond the muscularis propria. The depth of each ulcer was determined by endoscopic ultrasonography and/or ordinary endoscopic findings. We assessed clinical features, age, gender, smoking habit, alcohol consumption, ulcer history, presence of H. pylori, gastric acid secretion, gastric emptying, serum gastrin level, healing rate, and recurrence rate. RESULTS: Patients with UL4-type ulcers had a higher rate of recurrence and a significantly higher incidence of H. pylori infection. Patients with hyperacidity and currently smoking or consuming alcohol were significantly more likely to have UL4-type ulcers than of UL2 or 3 ulcers. Furthermore, a close relationship was recognized between recurrence, intractability and deeply excavated ulcers. Ulcer depth was not correlated significantly with any of the following factors: 1) patient's profile; including gender and hemorrhagic symptoms; 2) gastric function; including gastric emptying and serum gastrin levels. CONCLUSIONS: Smoking, alcohol consumption, recurrence of ulcers, hyperacidity and H. pylori infections are important factors associated with deep ulcers.

Female↗

Lipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia.

Expression of neurotrophins in pure microglia cultured from embryonic rat brain and the effects of lipopolysaccharide (LPS) on the expression were investigated. In untreated cultures, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT)-4/5 mRNAs were detected by use of reverse transcriptase-polymerase chain reaction but NT-3 mRNA was not. LPS stimulation caused a marked increase in BDNF mRNA expression in addition to a slight increment of the NT-4/5 mRNA level; however, the NGF mRNA level was not affected. LPS also increased BDNF-like immunoreactivity in cultured microglia, an action consistent with an elevation of BDNF mRNA. These results demonstrate that LPS stimulates synthesis of BDNF and probably NT-4/5, specific ligands for tyrosine kinase receptor TrkB, suggesting that activated microglia, which appear in the damaged brain, participate in neuronal regeneration via production of such neurotrophins.

Animals↗

Prostaglandin E1 potentiation of the spontaneous phasic contraction of rat isolated portal vein by a cyclopiazonic acid-sensitive mechanism.

1. The effect of prostaglandin E1 (PGE1) on the spontaneous phasic contraction of the rat isolated portal vein was studied. 2. The isolated portal vein exhibited spontaneous phasic contractions. Removal of Ca2+ from Krebs-Ringer solution or application of nifedipine abolished the spontaneous contraction, indicating that the contraction depends exclusively on Ca2+ influx through L-type Ca2+ channels. On the other hand, cyclopiazonic acid (CPA), a specific inhibitor of Ca(2+)-ATPase of sarcoplasmic reticulum (SR) increased the amplitude of the contractions, suggesting that the SR regulates the spontaneous contractions negatively by sequestration of Ca2+ entering through L-type Ca2+ channels and buffering the rise in cytosolic Ca2+. 3. PGE1 increased the amplitude of the spontaneous contraction in a concentration-dependent manner without affecting the resting tension. The effect was completely abolished by nifedipine. Bay K 8644 and phenylephrine (PE) also increased the amplitude of the contraction in a concentration-dependent manner. PGE1 at a concentration of 1 microM. Bay K 8644 at 100 nM and PE at 30 nM doubled the amplitude, respectively. 4. Pretreatment with 1 microM CPA abolished the effect of PGE1, but the effects of Bay K 8644 and PE were not inhibited by pretreatment with CPA. In contrast, 10 microM ryanodine attenuated the effect of PE without affecting the contractile effect of PGE1. 5. When the SR was depleted of Ca2+ by repeated applications of caffeine in a nominally Ca(2+)-free Krebs-Ringer solution, it took about 120 s to restore the spontaneous contraction after addition of Ca2+ into the solution. In CPA-treated veins, the time taken to restore the contraction was shortened significantly. Pretreatment with 1 microM PGE1 shortened the time to the same extent as pretreatment with CPA did. 6. These results suggest that PGE1 increases the amplitude of the spontaneous phasic contraction by a different mechanism from those by which PE and Bay K 8644 increase it. Inhibition of Ca(2+)-ATPase of the SR might be involved in the vasoactive effect of PGE1.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Olfactory evoked potential produced by electrical stimulation of the human olfactory mucosa.

Most physiological studies of the human olfactory system have concentrated on the cortical level; the olfactory bulbar level has been studied rarely. We attempted to stimulate the human olfactory mucosa by electrical pulse to detect the bulbar potentials. Electrical stimulation (2 mA, 0.5 ms) of the human olfactory mucosa evoked a change in potential recorded from the frontal sector of the head. A negative peak of the evoked potential that occurred at 19.4 ms (grand means, n = 5) after stimulation was the clearest. The highest amplitude of the potential was recorded from the frontal sector of the head on the stimulated side. Our findings were similar to the experimental results obtained from the olfactory bulbs of animals. This evoked potential was considered to be the human olfactory bulbar potential. When the subjects were stimulated by applying electricity to the olfactory mucosa, no sensation of smell occurred even though evoked potentials were recorded. Evoked potentials were recorded only when the stimulating electrode was located in the olfactory cleft. When the stimulating electrode was outside the olfactory cleft, the stimulation caused pain. The trigeminal nerve seemed to be stimulated by electricity. Olfactory evoked potentials produced by the electrical stimulation of the human olfactory mucosa should aid the research on human olfactory physiology, and may be applicable to clinical tests of olfactory dysfunction.

Electric Stimulation↗

Cytotoxicity and motility of Helicobacter pylori.

To clarify the relationship between interleukin-8 (IL-8) production and virulent factors, we examined the motility and cytotoxicity of H. pylori, suggested to be a major cause of chronic gastritis and peptic ulcers. Our results demonstrated that among cytotoxic strains of H. pylori, high-motility strains induced more IL-8 than low-motility strains. There was no correlation between cytotoxicity and motility of H. pylori. Four restriction fragment length polymorphism (RFLP) patterns were observed in the flaA PCR products. There was no correlation between flaA RFLP and motility. In conclusion, our findings suggest that both cytotoxicity and motility are virulent factors in the pathogenesis of gastric mucosal injury.

Animals↗

cDNA cloning and characterization of rat C5a anaphylatoxin receptor.

Activation of the complement cascade plays an essential role in the early stages of inflammation. C5a and its receptor are particularly active in anaphylaxis. To determine the pathological roles played by C5a and C5a receptor (C5aR) in rats, we cloned C5aR cDNA and analyzed distribution of its mRNA in various organs including lung from an LPS-stimulated rat. Furthermore, we generated a polyclonal antiserum which specifically recognizes rat C5aR, as confirmed by its specific interaction with cells transfected with rat C5aR cDNA.

Animals↗

Analysis of interleukin-8 secretion induced by Helicobacter pylori from the gastric epithelial cell line MKN45: a mechanism independent of the intensity of cytotoxicity.

Interleukin (IL)-8, a potent chemoattractant and activator of neutrophils, has been implicated to have a major role in the pathogenesis of gastric mucosal injury by Helicobacter pylori infection. We examined the relationship between cytotoxicity and IL-8 secretion induced by H. pylori. Furthermore, whether the vacuolating cytotoxin of H. pylori mediates IL-8 secretion from gastric epithelial cell lines was examined. Among the inflammatory cytokines, messages for IL-6, IL-8 and transforming growth factor-beta 1 were produced by gastric cancer (MKN45) cells in response to exposure to the cytotoxic strain of H. pylori. MKN45 incubated with the viable cytotoxic strain of H. pylori secreted IL-8. In contrast, the supernatant of neither the cytotoxic nor the non-cytotoxic strain induced IL-8 secretion. There was no correlation between IL-8 secretion and the intensity of cytotoxicity. In conclusion, these findings suggest that IL-8 secretion from MKN45 induced by H. pylori is mediated by factors other than cytotoxicity.

Bacterial Proteins↗

Activity of H(+)-ATPase in ruminal bacteria with special reference to acid tolerance.

Batch culture experiments showed that permeabilized cells and membranes of Ruminococcus albus and Fibrobacter succinogenes, acid-intolerant celluloytic bacteria, have only one-fourth to one-fifth as much H(+)-ATPase as Megasphaera elsdenii and Streptococcus bovis, which are relatively acid tolerant. Even in the cells grown in continuous culture at pH 7.0, the acid-intolerant bacteria contained less than half as much H(+)-ATPase as the acid-tolerant bacteria. The amounts of H(+)-ATPase in the acid-tolerant bacteria were increased by more than twofold when the cells were grown at the lowest pH permitting growth, whereas little increase was observed in the case of the acid-intolerant bacteria. These results indicate that the acid-intolerant bacteria not only contain smaller amounts of H(+)-ATPase at neutral pH but also have a lower capacity to enhance the level of H(+)-ATPase in response to low pH than the acid-tolerant bacteria. In addition, the H(+)-ATPases of the acid-intolerant bacteria were more sensitive to low pH than those of the acid-tolerant bacteria, although the optimal pHs were similar.

Animals↗

Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model.

BACKGROUND: Helicobacter pylori is a bacterium which causes gastric inflammatory diseases. Oral inoculation of H pylori usually results in only a temporary colonisation without a successful infection in the stomach of conventional mice in which lactobacilli are the predominant indigenous bacteria. AIM: To determine whether lactobacilli exert an inhibitory effect on colonisation by H pylori in the stomach. METHODS: The effects of H pylori on attachment to murine and human gastric epithelial cells and the H pylori mediated release of interleukin-8 (IL-8) by these cells were examined in vitro. Lactobacillus salivarius infected gnotobiotic BALB/c mice and control germ free mice were inoculated orally with H pylori to examine whether L salivarius can inhibit colonisation by H pylori. RESULTS: L salivarius inhibited both the attachment and IL-8 release in vitro. H pylori could not colonise the stomach of L salivarius infected gnotobiotic BALB/c mice, but colonised in large numbers and subsequently caused active gastritis in germ free mice. In addition, L salivarius given after H pylori implantation could eliminate colonisation by H pylori. CONCLUSION: These findings suggest the possibility of lactobacilli being used as probiotic agents against H pylori.

Animals↗

Synthesis and antitumor activity of novel benzophenone derivatives.

Novel benzophenone derivatives were synthesized and screened for cytotoxic and antitumor activity. Friedel-Crafts condensation was employed to construct the benzophenone skeleton. Among the compounds synthesized, morpholino and thiomorpholino benzophenones 3a-d exhibited potent cytotoxic activity against P388 murine leukemia and PC-6 human lung carcinoma cells in vitro, and compounds 3a, 3c, and 3j, when administered intraperitoneally, showed significant antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice.

Animals↗

Characterization of 30-kDa fragments derived from beta-conglycinin degradation process during germination and seedling growth of soybean.

The degradation process of beta-conglycinin, a vicilin-type glycosylated storage protein of soybean seeds, during germination and seedling growth was examined by concanavalin A blotting combined with polyacrylamide gel electrophoresis. We detected and analyzed the structures of key intermediary fragments of 30 kDa derived from beta-conglycinin degradation, they were proved to be single-domain type subunits of beta-conglycinin. We show here a degradation process of beta-conglycinin: beta-conglycinin is subjected to limited proteolysis at exposed regions on the molecular surface, like domain junctions, generating 30-kDa single-domain fragments before non-specific proteolysis.

Amino Acid Sequence↗

Flagellin gene diversity among Helicobacter pylori strains and IL-8 secretion from gastric epithelial cells.

BACKGROUND: To clarify the pathological functions of the virulence factors of Helicobacter pylori, a comparative analysis was carried out on the relationship between motility, flagellar gene polymorphism, vacuolating cytotoxin (VT) production and interleukin-8 (IL-8) induction. METHODS: Twenty-five strains were examined for restriction fragment length polymorphism (RFLP) of the flagellin gene. Motility was measured using semisolid agar plates. Cytotoxicity was assayed using RK-13 cells. IL-8 secretion was assessed by the enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: H. pylori was classified into four groups according to their flagellar RFLP. No differences were noted in motility or VT production among the four groups, but a significant difference was noted in IL-8 induction. In addition, highly motile strains produced more IL-8. CONCLUSION: This flagellar genetic polymorphism may be associated with IL-8 induction.

Animals↗

The role of histamine in ethanol-induced gastric mucosal injury in the rat.

It has been suggested that changes in the micro circulatory system are related to the early production of acute gastric mucosal injury and inflammatory factors such as prostaglandins, histamine, etc., have been considered as contributing to the development of the injury. We assessed the permeability of the gastric mucosa in rats with ethanol-induced acute mucosal injury by measuring the leakage rate of 51chronium-ethylene-diamine-tetraacetic acid (51Cr-EDTA) into the gastric juice. Histamine concentrations in the gastric mucosa was measured by high performance liquid chromatography. The enterochromaffin-like (ECL) cell counts in the gastric mucosa was performed following histamine staining with an enzyme-labeled antibody, and the histamine released due to degranulation was observed. We also investigated the kinetics of endogenous histamine in the gastric mucosa. Five minutes after the administration of ethanol, an increase in permeability, an increase in histamine concentration, and a decrease in ECL cell count were found in the gastric mucosa. These results suggest that endogenous histamine in the gastric mucosa is closely related to the early development of acute gastric mucosal injury.

Animals↗